Therapy of Diabetic Renal Disease

Friedman, Eli A.

doi:10.1007/978-1-4613-3807-9_27

Cited by 2 publications

(2 citation statements)

References 20 publications

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“…A ccelerated atherosclerosis and diabetic microvascular disease make diabetes a leading cause of coronary artery disease and a major cause of blindness and renal failure (1)(2)(3). Altered platelet function, such as hypersensitivity of platelets to collagen, is prevalent in diabetes and may participate in the pathogenesis of diabetic vascular complications by promoting microthrombus formation (4,5).…”

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confidence: 99%

Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

et al. 2001

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Alteration of platelet function contributes to microthrombus formation and may play an important role in the pathogenesis of diabetic micro-and macroangiopathies. However, the molecular mechanism for platelet dysfunction observed in patients with diabetes has not been fully elucidated. In this study, the direct effects of hyperglycemia on platelet function in vitro were investigated. Hyperglycemia increased reactive oxygen species generation in human platelets, and this effect was additive with that of collagen. Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial electron transport chain complex II, and carbonyl cyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, completely prevented the effects of hyperglycemia, suggesting that reactive oxygen species arise from the mitochondrial electron transport chain. Hyperglycemia potentiated both platelet aggregation and the subsequent release of platelet-derived growth factor AB induced by a nonaggregating subthreshold concentration of collagen, which were also completely inhibited by TTFA or CCCP. Furthermore, hyperglycemia was found to inhibit protein tyrosine phosphatase (PTP) activity and increase phosphorylation of the tyrosine kinase Syk in platelets exposed to collagen. Hyperglycemia-induced PTP inhibition and Syk phosphorylation were found to be completely prevented by TTFA, CCCP, or Mn(III)tetrakis (4-benzoic acid) porphyrin, a stable cell-permeable superoxide dismutase mimetic. These results suggest that hyperglycemiainduced mitochondrial superoxide generation may play an important role in platelet dysfunction observed in patients with diabetes.

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Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

et al. 2001

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“…Diabetes mellitus is a chronic metabolic disease associated with microvascular complications, such as nephropathy and retinopathy. Diabetic nephropathy is associated with both glomerular expansion and renal hypertension ( 14). Diabetic retinopathy involves retinal microaneurysms, increased capillary proliferation, and abnormal vessel structures leading to retinal detachment and blindness ( 15).…”

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confidence: 99%

Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes.

Halvorsen

Bursell²,

Wilkison³

et al. 1993

J. Clin. Invest.

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1-Butyryl-glycerol (monobutyrin) is a simple lipid product of adipocytes with angiogenic activity. Recent studies have shown that the biosynthesis ofthis compound is tightly linked to lipolysis, a process associated with changes in blood flow. We now present data indicating that monobutyrin is an effective vasodilator of rodent blood vessels using a fluorescent retinal angiogram assay. The vasodilatory activity of monobutyrin is potent (ED50 = 3.3 X 10-7 M), dose dependent, and stereospecific.Because diabetes represents a catabolic, lipolytic state with numerous vascular complications, we examined the action and regulation of monobutyrin in insulin-deficient diabetic rats. Serum levels of monobutyrin in streptozotocin-induced diabetic rats were greatly elevated compared to normal animals. At the same time, the retinal vessels of the diabetic animals develop a resistance to the vasodilatory activity of monobutyrin. These results demonstrate a role for monobutyrin in the control of vascular tone and suggest a possible involvement in the pathology of diabetes. (J. Clin. Invest. 1993. 92:2872-2876

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Therapy of Diabetic Renal Disease

Cited by 2 publications

References 20 publications

Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

Hyperglycemia Potentiates Collagen-Induced Platelet Activation Through Mitochondrial Superoxide Overproduction

Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes.

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